Comparative pharmacokinetics and pharmacodynamics of a PEGylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children

Abstract

Objective

Recombinant human growth hormone (rhGH) replacement therapy in children generally requires daily subcutaneous (sc) injections, which may be inconvenient for patients. Jintrolong^® is a PEGylated rhGH with the purpose of weekly sc injections. The aim of the current study was to examine the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple sc doses of Jintrolong^® vs daily doses of rhGH.

Design and methods

Twelve children with growth hormone deficiency participated in this single-center, open-label, crossover Phase I trial. All subjects received daily sc injections of rhGH at 0.0286 mg/kg/d for 7 days, followed by a 4-week washout period and six weekly doses of Jintrolong^® at 0.2 mg/kg/w.

Results

In comparison with rhGH, sc injection of Jintrolong^® produced a noticeably higher C_max, significantly longer half-life (t_1/2), and slower plasma clearance, signifying a profile suitable for long-term treatment. The ratio of the area under the concentration vs time curve (AUC) after the seventh and first injections (AUC_(0–∞)7th/AUC_(0–∞)1st) of rhGH was 1.02, while the AUC_(0–∞)6th/AUC_(0–∞)1st of Jintrolong ^® was 1.03, indicating no accumulation of circulating growth hormone. There was no significant difference in the change in insulin-like growth factor-1 expression produced by 7 days of sc rhGH and weekly Jintrolong^® injections. There were no severe adverse events during the trial.

Conclusion

The elimination rate of Jintrolong^® was slower than that of sc rhGH. No progressive serum accumulation of Jintrolong^® was found. The changes in insulin-like growth factor-1 expression produced by rhGH and Jintrolong^® were comparable, indicating similar pharmacodynamics. Our results demonstrate that Jintrolong^® is suitable for long-term growth hormone treatment in children with growth hormone deficiency.

Keywords:

• long-acting growth hormone
• phase I
• multiple-dose

Supplementary material

Table S1 Pharmacokinetic parameters for rhGH and Jintrolong^® in healthy adults

Acknowledgments

This study was supported by 12th five-year plan national key technology R&D program (2012BAI09B04) and Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT1131).

Disclosure

The authors report no conflicts of interest in this work.